atopic IgE-mediated allergic disorder

Summary

atopic IgE-mediated allergic disorder (MONDO:0005202) is a disease with 3 cohort genes (6 GWAS associations across 8 studies).

At a glance

• Cohort genes: 3
• GWAS associations: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atopic IgE-mediated allergic disorder
Mondo ID	MONDO:0005202
EFO	EFO:0002686
SNOMED CT	115665000
UMLS	C1706410
MedGen	739536
Is cancer (heuristic)	no

Data availability: 6 GWAS associations (8 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › hypersensitivity reaction disease › allergic disease › atopic IgE-mediated allergic disorder

Related subtypes (11): allergic respiratory disease, drug allergy, gastrointestinal allergy, latex allergy, atopic eczema, eye allergy, vulvovaginitis, allergic seminal, allergic otitis media, alpha-gal syndrome, venom allergy, food allergy

Genetics & variants

GWAS landscape

6 GWAS associations across 8 studies. Top hits map to 6 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr9:6255967	4e-18		C	0.6
rs1255383	9e-10	ZNF37BP, ZNF37BP	C
rs2483695	2e-09	ZNF33B	A
rs4916831	7e-09	ADGRV1	G	1.41
rs4952590	2e-06	PKDCC	?	1.92
rs6056732	3e-06	PAK5	C	1.64

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90081463	Backman JD	2021	46,691	313,235	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90085449	Backman JD	2021	46,691	313,235	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST000870	Wan YI	2010	1,083	2,770	A genome-wide association study to identify genetic determinants of atopy in subjects from the United Kingdom.
GCST006040	Sugier PE	2017	925	0	A novel role for ciliary function in atopy: ADGRV1 and DNAH5 interactions.
GCST001075	Andiappan AK	2011	515	0	Genome-wide association study for atopy and allergic rhinitis in a Singapore Chinese population.
GCST000540	Castro-Giner F	2009	75	0	A pooling-based genome-wide analysis identifies new potential candidate genes for atopy in the European Community Respiratory Health Survey (ECRHS).
GCST90258648	Lee S	2022	0	0	Zinc finger protein 33B demonstrates sex-interaction with atopy-related markers in childhood asthma.
GCST90258649	Lee S	2022	0	0	Zinc finger protein 33B demonstrates sex-interaction with atopy-related markers in childhood asthma.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	6

MAF distribution

Bucket	Variants
common (>=0.05)	5
low_freq (0.01-0.05)	0
rare (<0.01)	1
unknown	0

Functional consequences

Consequence	Count
intron_variant	5
unknown	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr9:6255967				0.005			4e-18	Tier 4: intronic/intergenic
rs1255383	10	42527140	A>C,T	0.05	intron_variant	ZNF37BP, ZNF37BP	9e-10	Tier 4: intronic/intergenic
rs2483695	10	42638205	T>A	0.05	intron_variant	ZNF33B	2e-09	Tier 4: intronic/intergenic
rs4916831	5	90916459	A>C,G	0.44	intron_variant	ADGRV1	7e-09	Tier 4: intronic/intergenic
rs4952590	2	42049781	C>T	0.14	intron_variant	PKDCC	2e-06	Tier 4: intronic/intergenic
rs6056732	20	9595973	C>A	0.09	intron_variant	PAK5	3e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ADGRV1	Orphanet:231178	Usher syndrome type 2
ADGRV1	Orphanet:36387	Genetic epilepsy with febrile seizure plus

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PAK6	HGNC:16061	ENSG00000137843	Q9NQU5	Serine/threonine-protein kinase PAK 6	gwas
ADGRV1	HGNC:17416	ENSG00000164199	Q8WXG9	Adhesion G-protein coupled receptor V1	gwas
PKDCC	HGNC:25123	ENSG00000162878	Q504Y2	Extracellular tyrosine-protein kinase PKDCC	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PAK6	Serine/threonine-protein kinase PAK 6	Serine/threonine protein kinase that plays a role in the regulation of gene transcription.
ADGRV1	Adhesion G-protein coupled receptor V1	G-protein coupled receptor which has an essential role in the development of hearing and vision.
PKDCC	Extracellular tyrosine-protein kinase PKDCC	Secreted tyrosine-protein kinase that mediates phosphorylation of extracellular proteins and endogenous proteins in the secretory pathway, which is essential for patterning at organogenesis stages.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	2	18.5×	0.008
GPCR	1	8.0×	0.120

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PAK6	Kinase	yes		CRIB_dom, Prot_kinase_dom, Kinase-like_dom_sf
ADGRV1	GPCR	yes		GPCR_2_secretin-like, Calx_beta, EPTP
PKDCC	Kinase	yes		Prot_kinase_dom, Kinase-like_dom_sf, FAM69_kinase_dom

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
entorhinal cortex	1
gingiva	1
gingival epithelium	1
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1
left ovary	1
left uterine tube	1
right ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PAK6	212	broad	marker	gingival epithelium, gingiva, entorhinal cortex
ADGRV1	196	broad	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland
PKDCC	238	ubiquitous	marker	right ovary, left ovary, left uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAK6	2,291
PKDCC	1,672
ADGRV1	1,658

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PAK6	Q9NQU5	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PKDCC	Q504Y2	82.96
ADGRV1	Q8WXG9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 3 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Activation of RAC1	1	407.9×	0.016	PAK6
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	184.2×	0.016	ADGRV1
RHOH GTPase cycle	1	154.3×	0.016	PAK6
RHOV GTPase cycle	1	142.8×	0.016	PAK6
RHOD GTPase cycle	1	102.0×	0.018	PAK6
CDC42 GTPase cycle	1	36.1×	0.041	PAK6
RAC1 GTPase cycle	1	30.5×	0.042	PAK6
Nervous system development	1	21.5×	0.052	ADGRV1
Developmental Biology	1	7.2×	0.134	ADGRV1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of bone mineralization	2	261.3×	8e-04	ADGRV1, PKDCC
maintenance of animal organ identity	1	1123.5×	0.011	ADGRV1
inner ear receptor cell differentiation	1	1123.5×	0.011	ADGRV1
negative regulation of Golgi to plasma membrane protein transport	1	936.2×	0.011	PKDCC
sensory perception of light stimulus	1	624.1×	0.011	ADGRV1
neuron projection arborization	1	624.1×	0.011	PAK6
self proteolysis	1	510.7×	0.012	ADGRV1
nervous system process	1	401.2×	0.012	ADGRV1
limb morphogenesis	1	351.1×	0.012	PKDCC
embryonic digestive tract development	1	330.4×	0.012	PKDCC
detection of mechanical stimulus involved in sensory perception of sound	1	312.1×	0.012	ADGRV1
inner ear receptor cell stereocilium organization	1	280.9×	0.012	ADGRV1
positive regulation of chondrocyte differentiation	1	267.5×	0.012	PKDCC
neuron projection extension	1	175.5×	0.017	PAK6
regulation of MAPK cascade	1	151.8×	0.018	PAK6
establishment of protein localization	1	144.0×	0.018	ADGRV1
peptidyl-tyrosine phosphorylation	1	140.4×	0.018	PKDCC
inner ear development	1	124.8×	0.018	ADGRV1
photoreceptor cell maintenance	1	119.5×	0.018	ADGRV1
lung alveolus development	1	117.0×	0.018	PKDCC
learning	1	93.6×	0.021	PAK6
bone mineralization	1	90.6×	0.021	PKDCC
roof of mouth development	1	82.6×	0.022	PKDCC
cellular response to calcium ion	1	66.9×	0.026	ADGRV1
cellular response to starvation	1	64.6×	0.026	PAK6
memory	1	61.1×	0.026	PAK6
locomotory behavior	1	59.8×	0.026	PAK6
multicellular organism growth	1	45.7×	0.032	PKDCC
cytoskeleton organization	1	44.2×	0.032	PAK6
skeletal system development	1	41.9×	0.032	PKDCC

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PAK6	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PAK6	13	4
ADGRV1	0	0
PKDCC	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	PAK6
RUXOLITINIB	4	PAK6
NERATINIB	4	PAK6
SUNITINIB	4	PAK6
LESTAURTINIB	3	PAK6
R-406	2	PAK6
AT-9283	2	PAK6
TOZASERTIB	2	PAK6
UCN-01	2	PAK6
BMS-754807	2	PAK6
KW-2449	1	PAK6
PF-03758309	1	PAK6
GSK-690693	1	PAK6

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PAK6	277	Binding:277

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PAK6	277

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

13 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	PAK6
RUXOLITINIB	4	PAK6
NERATINIB	4	PAK6
SUNITINIB	4	PAK6
LESTAURTINIB	3	PAK6
R-406	2	PAK6
AT-9283	2	PAK6
TOZASERTIB	2	PAK6
UCN-01	2	PAK6
BMS-754807	2	PAK6
KW-2449	1	PAK6
PF-03758309	1	PAK6
GSK-690693	1	PAK6

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PAK6
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	2	ADGRV1, PKDCC
E	Difficult family or no structure, no drug	0

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ADGRV1	0	—
PKDCC	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.